Tangluoning, a traditional Chinese medicine, attenuates in vivo and in vitro diabetic peripheral neuropathy through modulation of PERK/Nrf2 pathway

Yang, Xinwei; Yao, Weijie; Liu, Haolong; Gao, Yanbin; Liu, Renhui; Xu, Liping

doi:10.1038/s41598-017-00936-9

Cited by 37 publications

(35 citation statements)

References 48 publications

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“…For example, Zhao et al found that Gaoshan Hongjingtian could control retinal capillary degeneration in rats with diabetic retinopathy (Yang et al, 2013). Additionally, refined-JinQi-JiangTang tablets are reported to reduce insulin resistance and ameliorate b cell function (Gao et al, 2014), while Tangluoning improves diabetic peripheral neuropathy via regulating the PERK/ Nrf2 pathway (Yang et al, 2017). Furthermore, our previous study reported that Shensong Yangxin Capsule improves DCM through influencing myocardial fibrosis .…”

Section: Discussionmentioning

confidence: 99%

“…DM is characterized by high blood glucose and leads to multiple complications including diabetic retinopathy, diabetic nephropathy, and diabetic neuropathy (Baba and Ishizaki, 1992;Chen et al, 2017;Hung et al, 2017;Ung et al, 2017). Additionally, refined-JinQi-JiangTang tablets are reported to reduce insulin resistance and ameliorate b cell function (Gao et al, 2014), while Tangluoning improves diabetic peripheral neuropathy via regulating the PERK/ Nrf2 pathway (Yang et al, 2017). Evidence indicates that Chinese traditional medicine and phytomedicine have beneficial effects on diabetic complications including DCM.…”

Section: Discussionmentioning

confidence: 99%

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Silymarin ameliorates diabetic cardiomyopathy via inhibiting TGF‐β1/Smad signaling

Meng

Yang

Wang

et al. 2018

Cell Biology International

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Diabetic cardiomyopathy (DCM) is the leading cause of morbidity and mortality in diabetes mellitus (DM) patients. Previous studies have shown that the transforming growth factor-beta 1 (TGF-b1)/Smad signaling pathway plays a key role in the development of myocardial fibrosis in DCM. Silymarin (SMN) is used clinically to treat liver disorders and acts by influencing TGF-b1. However, the possible effects of silymarin on DCM remain to be elucidated. In our study, the DM animal model was induced by streptozotocin (STZ) injection. Fasting blood glucose level was measured, and the structure and function of the heart were measured by hematoxylin and eosin (H&E) and Masson staining, echocardiography, and transmission electron microscopy (TEM). Western blot was used to detect the expression of TGF-b1, Smad2/3, phosphorylation Smad2/3(p-Smad2/ 3), and Smad7. Our results showed that silymarin downregulated blood glucose level and significantly improved cardiac fibrosis and collagen deposition in DM rats detected by H&E, Masson staining, and TEM assays. The echocardiography results showed that silymarin administration attenuated cardiac dysfunction in DM rats. Additionally, compared with untreated DM rats, levels of TGF-b1 and p-Smad2/3 were decreased, whereas Smad7 was increased following silymarin administration. These data demonstrate that silymarin ameliorates DCM through the inhibition of TGF-b1/Smad signaling, suggesting that silymarin may be a potential target for DCM treatment.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Silymarin ameliorates diabetic cardiomyopathy via inhibiting TGF‐β1/Smad signaling

Meng

Yang

Wang

et al. 2018

Cell Biology International

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“…Several lines in the literature indicate that PERK-activated Nrf2 signaling transduction displays pivotal roles in cellular protection. For instance, Yang et al report that Tang-Luo-Ning treatment obviously mitigates hyperglycemia-provoked Schwann cells death via upregulating PERK/Nrf2 cascade [23]. e mechanism underlying the fact that Botrysphin D relieves the impairment of lung epithelial cells caused by arsenic is attributed to the activation of the PERK-mediated Nrf2 pathway [24].…”

Section: Discussionmentioning

confidence: 99%

PERK Overexpression-Mediated Nrf2/HO-1 Pathway Alleviates Hypoxia/Reoxygenation-Induced Injury in Neonatal Murine Cardiomyocytes via Improving Endoplasmic Reticulum Stress

Wang

Lü

Chen

et al. 2020

BioMed Research International

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Reperfusion processes following acute myocardial infarction (AMI) have been reported to induce additional cardiomyocyte death, known as ischemia-reperfusion (I/R) injury. Endoplasmic reticulum (ER) stress is reported to be involved in the development of I/R injury. There is evidence that PERK exerts beneficial roles in alleviating ER stress. Here, we investigated whether upregulation of PERK improved cardiomyocytes injury induced by I/R. Specific siRNAs or adenovirus vectors were incubated with isolated neonatal cardiomyocytes (NCMs) to regulate expression levels of target genes including PERK, Nrf2, and HO-1. Afterwards, hypoxia and subsequent reoxygenation (H/R) administration was performed as the in vitro model of I/R injury. MTT assay showed that H/R intervention decreased the viability of cells, yet PERK overexpression increased the cellular proliferative rate. Moreover, the upregulation of Nrf2 or HO-1 elevated the growth rate of cells, while gene silencing of Nrf2 or HO-1 reduced the viability of NCMs treated with PERK-rAAV9. In addition, we observed that the apoptotic index of cells with H/R stimulation was reduced when NCMs were pretreated with PERK-rAAV9, Nrf2-rAAV9, or HO-1-rAAV9. After cells were incubated with Nrf2-siRNA or HO-1-siRNA, the upregulation of PERK had no roles in affecting the apoptosis rate of NCMs damaged by H/R. Then, our findings indicated that there was a level decrease of GRP78, CRT, CHOP, and Caspase-12 in NCMs of the PERK-rAAV9 group compared to that of the H/R group. Both Nrf2 overexpression and HO-1 upregulation reduced the expression of ER stress-related proapoptotic factors, yet the expression suppression of Nrf2 and HO-1 increased levels of GRP78, CRT, CHOP, and Caspase-12 in NCMs treated with PERK-rAAV9. Taken together, our results suggested that the effects of PERK against H/R injury might be attributed to the upregulation of Nrf2/HO-1 cascade, followed by the inhibition of ER stress-related apoptotic pathway.

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“…Recently, CHM has been playing a progressively more important role in the treatment of diseases with complex pathogenesis and symptoms, including DPN. Both clinical trials and animal tests have proved the efficacy of CHM in the treatment of DPN, but more studies are needed to accumulate further evidence [15][16][17].…”

Section: Introductionmentioning

confidence: 99%

Efficacy of Chinese Herbal Medicine in the Treatment of Moderate-Severe Painful Diabetic Peripheral Neuropathy: A Retrospective Study

Zheng

Fan

Lin

et al. 2019

Journal of Diabetes Research

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Painful diabetic peripheral neuropathy (pDPN) is a debilitating complication of diabetes. The aim of this retrospective study was to investigate the effectiveness of a Chinese herbal medicine regimen—the modified Huangqi Guizhi Wuwu Decoction (HGWD)—in the treatment of moderate-severe pDPN. The primary objective was to estimate the improvement in neuropathic pain severity. The secondary objective was to assess the response of common symptoms to the treatment. The change in patients’ blood glucose level during the whole treatment was also evaluated. By searching through our medical records of all the diabetic patients from January 2006 to January 2012, we identified and enrolled 30 moderate and severe pDPN patients in the study, for whom the treatment of neuropathic pain by regular pharmacotherapies had failed. The modified HGWD treatment was administered orally twice a day for 6 months. The numerical rating scale (NRS) level at month 6 was 2.57±2.30, significantly improved compared with the baseline level of 6.03±1.83 (P<0.05). The amelioration of 3 common symptoms, namely, limb pain, limb numbness, and insomnia, was evident, and the major response of common symptoms at month 6 including limb pain, insomnia, and limb coldness was significantly increased compared with the results at month 3 (P<0.05). Moreover, 2-hour postprandial blood glucose (2hPG) level decreased from 10.77±1.29 mmol/L at baseline to 9.66±0.60 mmol/L at month 6 (P<0.05). No serious adverse events occurred throughout the treatment period. The modified HGWD was effective in the treatment of moderate and severe pDPN and can thus be offered as a new alternative treatment option for pDPN patients who failed to respond to regular pharmaceutical therapies.

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Tangluoning, a traditional Chinese medicine, attenuates in vivo and in vitro diabetic peripheral neuropathy through modulation of PERK/Nrf2 pathway

Cited by 37 publications

References 48 publications

Silymarin ameliorates diabetic cardiomyopathy via inhibiting TGF‐β1/Smad signaling

Silymarin ameliorates diabetic cardiomyopathy via inhibiting TGF‐β1/Smad signaling

PERK Overexpression-Mediated Nrf2/HO-1 Pathway Alleviates Hypoxia/Reoxygenation-Induced Injury in Neonatal Murine Cardiomyocytes via Improving Endoplasmic Reticulum Stress

Efficacy of Chinese Herbal Medicine in the Treatment of Moderate-Severe Painful Diabetic Peripheral Neuropathy: A Retrospective Study

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